The mammalian olfactory system consists of at least two functionally distinct organs, the main olfactory epithelium and the vomeronasal organ (VNO). The VNO, a pair of tubular structures at the rostral end of the nasal cavity, is thought to mediate detection of pheromones, chemical signals that regulate reproductive and social behavior and neuroendocrine status. Sensory transduction in the VNO is distinct from that in the main olfactory epithelium, and remains poorly understood. The experiments described in this grant will test the hypothesis that sensory transduction in the VNO is mediated by a signaling pathway similar to that which mediates phototransduction in invertebrates. In support of this hypothesis, we have recently found a VNO- specific homolog (TRP2) of the Drosophila light-activated channel (dTRP) that is highly localized to sensory microvilli of rat vomeronasal sensory neurons. The proposed research is aimed at elucidating the role of the TRP2 channel in vomeronasal sensory transduction, and in VNOmediated behaviors. A central goal of this work is to identify second messenger pathways that activate TRP2. Extensive studies in Drosophila, suggest that activation of dTRP is downstream of phospholipase C, but the direct stimulus for opening dTRP channels is not known. We will use techniques of patch-clamp recording and ratiometric Ca++ imaging in heterologous cell types to study gating of TRP2 in response to receptor-mediated stimulation of phospholipase C and direct application of putative second messengers. A second goal is to identify additional components of the sensory transduction cascade. The candidate, Dr. Liman, has recently joined the faculty at the University of Southern California, where she is an assistant professor. This ISA will greatly enhance the candidate's career development by allowing her much needed time to set up a strong research program, involving a variety of sophisticated techniques. The candidate is an experienced electrophysiologist as well as a molecular biologist, and the research proposed will take advantage of her expertise in these disparate techniques to tackle basic questions in the biology of the vomeronasal system.